Kolbe–Schmitt reaction

"Kolbe process" redirects here. For the electrochemical decarboxylation/dimerization reaction, see Kolbe electrolysis.

Kolbe–Schmitt reaction
Named after	Hermann Kolbe Rudolf Schmitt
Reaction type	Addition reaction
Identifiers
Organic Chemistry Portal	kolbe-schmitt-reaction
RSC ontology ID	RXNO:0000182

The Kolbe–Schmitt reaction or Kolbe process (named after Hermann Kolbe and Rudolf Schmitt) is a carboxylation chemical reaction that proceeds by treating phenol with sodium hydroxide to form sodium phenoxide, ^[1] then heating sodium phenoxide with carbon dioxide under pressure (100 atm, 125 °C), then treating the product with sulfuric acid. The final product is an aromatic hydroxy acid which is also known as salicylic acid (the precursor to aspirin). ^{[2] [3] [4] [5]}

The Kolbe–Schmitt reaction

By using potassium hydroxide, 4-hydroxybenzoic acid is accessible, an important precursor for the versatile paraben class of biocides used e.g. in personal care products.

The methodology is also used in the industrial synthesis of 3-hydroxy-2-naphthoic acid; the regiochemistry of the carboxylation in this case is sensitive to temperature. ^[6]

Reaction mechanism

The Kolbe–Schmitt reaction proceeds via the nucleophilic addition of a phenoxide, classically sodium phenoxide (NaOC₆H₅), to carbon dioxide to give the salicylate. The final step is the reaction (protonation) of the salicylate anion with an acid to form the desired salicylic acids (ortho- and para- isomers).

Kolbe–Schmitt reaction

(animation)

Homogeneous Kolbe-Schmitt Reaction

A modification of the classical solid-phase Kolbe-Schmitt reaction, where the solvent play a role of active media dissolving reagents and solvating cations and anions. Typical solvents for homogeneous Kolbe-Schmitt reaction are DMSO, DMF, HMPTA. ^[7] Carboxylation of sodium and potassium phenoxides in solution of DMSO proceeds under milder temperature (100 °C) with high para-regioselectivity (up to 97:3) producing 4-hydroxybenzoic acid (4HBA) instead of 2-hydroxybenzoic (salicylic) acid (SA). ^[8] Addition into the reaction mixture of basic sodium salts like mesytolate, isopropylcarbonate, tert-butylcarbonate increase the chemical yield of a mixture 4HBA&SA up to two fold.

Screening of various metal cations, different substituted phenoxides, solvents (DMSO and DMF) in combination with activating additive (mesytolate) provide a general and effective method of homogeneous carboxylation. ^[9]

Homogeneous carboxylation

Particularly, rhubidium and cesium salts directed carboxylation into para-position of phenoxides with unprecedented regioselectivity. It is suggested that mechanism of the reaction involes molecular associates which responsible for decreasing of activation energy barrier of carboxylation. Carboxylation of potassium phenoxide was shown to occur rapidly under atmospheric CO₂ pressure at 113°C in a gasometric study.

References

1. C. S. Marvel; A. L. Tanenbaum (1929). "γ-Phenoxypropyl Bromide". Org. Synth. 9: 72. doi:10.15227/orgsyn.009.0072.
2. Hermann Kolbe (1860). "Ueber Synthese der Salicylsäure" [On the synthesis of salicylic acid]. Annalen der Chemie und Pharmacie . 113 (1): 125–127. doi:10.1002/jlac.18601130120. English translation by Matthew Johnathan Leonard.
3. R. Schmitt (1885). "Beitrag zur Kenntniss der Kolbe'schen Salicylsäure Synthese" [Contribution to [our] knowledge of Kolbe's synthesis of salicylic acid]. Journal für Praktische Chemie . 2nd series. 31 (1): 397–411. doi:10.1002/prac.18850310130.
4. A. S. Lindsey and H. Jeskey (1957). "The Kolbe-Schmitt Reaction". Chem. Rev. 57 (4): 583–620. Bibcode:1957ChRv...57..583L. doi:10.1021/cr50016a001. (Review)
5. R. T. Morrison and R. N. Boyd (1983). Organic Chemistry (4th ed.). Allyn and Bacon. p.  976-7. ISBN   0-205-05838-8.
6. Gerald Booth (2005). "Naphthalene Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_009. ISBN   3-527-30673-0..
7. Hirao, I. (1976). "Use of Carbon Dioxide in Industrial Organic Chemistry - The Behavior of Carbon Dioxide in the Kolbe-Schmitt Reaction". J. Synth. Org. Chem. Japan . 34 (5): 326–332. doi: 10.5059/yukigoseikyokaishi.34.326 . (Review)
8. Merzliakov, D.A.; Alexeev, M.S.; Topchiy, M.A.; Yakhvarov, D.G.; Kuznetsov, N.Y.; Maximov, A.L.; Beletskaya, I.P. (2025). "Development of Homogeneous Carboxylation of Phenolates via Kolbe–Schmitt Reaction". Molecules . 30 (2): 248. doi: 10.3390/molecules30020248 . PMC   11767310 .
9. Merzliakov, D.A.; Alexeev, M.S.; Topchiy, M.A.; Yakhvarov, D.G.; Kuznetsov, N.Y.; Maximov, A.L.; Beletskaya, I.P. (2026). "Synthesis of Hydroxyaromatic Carboxylic Acids via Homogeneous Kolbe-Schmitt Carboxylation of Phenoxides". Molecules . 31 (2): 239. doi: 10.3390/molecules31020239 .